Characterization of the 3D nanostructure of amorphous solid dispersions
| dc.contributor.author | Olsson, Martina | |
| dc.contributor.department | Chalmers tekniska högskola / Institutionen för fysik | sv |
| dc.contributor.examiner | Matic, Alexandar | |
| dc.contributor.supervisor | Matic, Alexandar | |
| dc.contributor.supervisor | Liebi, Marianne | |
| dc.date.accessioned | 2020-06-16T09:17:20Z | |
| dc.date.available | 2020-06-16T09:17:20Z | |
| dc.date.issued | 2020 | sv |
| dc.date.submitted | 2019 | |
| dc.description.abstract | Dissolution enhancing formulation strategies are getting increasingly important for the pharmaceutical industry as many new upcoming drugs present a poor water solubility. A low solubility decreases the bioavailability of the drug and diminish the therapeutic effect. One method that have shown successful results of achieving increased solubility is the formulation strategy of amorphous solid dispersions which are compound that consist of an amorphous drug dispersed in a polymer carrier. Despite successful pharmaceutical compounds being produced these systems are not fully understood, and their formulation are still largely empirical. One of the key issues is to understand the morphology of the system and how it affects the pharmaceutical performance to enable a rational design process. In this thesis the nanostructure is evaluated for a model system of amorphous solid dispersions consisting of Felodipine in ethyl cellulose. Samples were prepared through hot melt extrusion and solvent casting with drug loads between 10-80 wt% to evaluate the effect of processing method and drug load on the morphology. In addition, a partly crystalline sample of hot melt extruded 50 wt% Carbamazepine in ethyl cellulose was used as a comparison. Ptychographic X-ray nanotomography was used as the main method together with scanning calorimetry (DSC) and X-ray-scattering (SAXS/WAXS). The nanotomography resolved the threedimensional morphology with a resolution of 100 nm and revealed a phase separation in all samples that were not detected with DSC and X-ray-scattering in the q-range accessible with a laboratory SAXS station. The different preparation methods created different morphologies and showed that the processing method have an effect on the phase separation mechanism. The solvent casted sample revealed a morphology from phase separation through nucleation and growth while the hot melt extruded samples showed a pattern characteristic for spinodal decomposition. The drug load had a minor effect on the extent of phase separation. A low amount of crystallinity was found in all Felodipine in ethyl cellulose samples and showed that all samples remained stable in the amorphous state during storage in ambient temperature and humidity over a time period of three months. The small fraction of crystallinity that was found were detected in the drug rich phase, indicating that phase separation is an onset for crystallization. | sv |
| dc.identifier.coursecode | TIFX61 | sv |
| dc.identifier.uri | https://hdl.handle.net/20.500.12380/300865 | |
| dc.language.iso | eng | sv |
| dc.setspec.uppsok | PhysicsChemistryMaths | |
| dc.subject | Amorphous solid dispersions | sv |
| dc.subject | ptychographic X-ray nanotomography | sv |
| dc.subject | phase separation | sv |
| dc.subject | 3D morphology | sv |
| dc.subject | Felodipine | sv |
| dc.title | Characterization of the 3D nanostructure of amorphous solid dispersions | sv |
| dc.type.degree | Examensarbete för masterexamen | sv |
| dc.type.uppsok | H | |
| local.programme | Applied physics (MPAPP), MSc |